Eye PPT

1. Dr. Avin Khushiramani
Junior Resident 1
Dept. of Ophthalmology
MIMER Medical College
Guide- Dr. Suneeta Jagtap
Presentation To IEC
Evaluation of Changes in Retinal Nerve Fibre
Layer Thickness (RNFL) using Optical Coherence
Tomography (OCT) in patients undergoing
ethambutol treatment.

2. Introduction
•Tuberculosis - a leading cause of death worldwide. India is the country with the highest estimated
number of TB cases (2.75 million), which accounts for 27% of the global burden. [1]
• In a revised national tuberculosis control programme in 2016, the WHO recommended switching from
a thrice weekly antitubercular treatment (ATT) regimen to a daily dose regimen. [2]
•It also extended the duration of ethambutol (EMB) intake from 2 to 6 months, leading to a markedly
increased cumulative dose of the same.
•The most serious adverse effect of ethambutol is optic neuropathy, which affects 22.5 people out of
every 1,000. (3)
•The toxic optic neuropathy typically manifests between 4 to 12 months after initiating the medication
and is known to be dose and duration-dependent.[6]
•This ethambutol optic neuropathy (EON) is reversible, however its delayed diagnosis can
cause permanent visual loss.[7][8][9]

3. • This warrants the need for investigations that will detect ocular changes leading to EON at an early stage so as
to prevent permanent visual loss.
• Optical coherence tomography (OCT), is a a non-contact, non-invasive technology diagnostic technique that
uses high-resolution images of retinal structures to detect subclinical optic nerve damage in the form of Retinal
Nerve Fibre Layer (RNFL) thinning.
• As per a study conducted, significant loss of temporal RNFL thickness (>20 um) was detected in 3% patients at
the end of 2 months when Thrice weekly regimen was in place.[12] However the amount of reduction is not
mentioned in this study.
• But with the new Daily Dose regimen the toxicity considering two parameters (Visual Evoked Response, RNFL
thinning) was detected in 46% patients at the end of 6 months according to another study .[13] However this
study doesn’t mention the number of people affected by RNFL thinning at the end of 4 months or 6 months of
treatment.

4. • Since there is lack of enough evidence regarding the change in RNFL thickness at the
end of 3 months of ethambutol treatment with this new daily dose regimen and to
determine the burden of toxicity at the end of 3 months of treatment i.e at an early
stage to prevent progression to Toxic optic neuropathy and hence irreversible vision
loss, this study has been planned with following aims and objectives.

5. Study implications
To detect RNFL thinning by OCT at an early stage in patients taking ethambutol in order
to prevent progression to toxic optic neuropathy and hence irreversible visual loss.

6. Aims and Objectives
Aim
• To detect changes in retinal thickness by OCT due to the use of ethambutol in the
treatment of tuberculosis patients.

7. Aims and Objectives
Specific objectives
• To evaluate changes in peripapillary Retinal Nerve Fibre Layer (RNFL) thickness in patients
undergoing ethambutol treatment.
• Correlation of degree of retinal nerve fibre layer thinning with visual acuity.

8. Materials and Methods
• Study setting - Study will be carried out in Ophthalmology OPD of A Tertiary Care Hospital
• Study design - Prospective Observational
• Study type - Purposive type
• Sampling procedure – Consecutive sampling
• Sample size calculation -
According to study conducted, considering the difference of 5 um between baseline RNFL
thickness and after 3 months of ethambutol treatment,
Type 1 alpha error - 0.05 and power of test at 8% i.e. Beta – 0.02
the minimum required sample size to detect the difference of 5 um is 73.
Sample size is calculated using Winpepi software.

9. Subject selection
Patients newly diagnosed with Pulmonary/Extrapulmonary Tuberculosis, reporting to Medicine OPD
and Chest and TB OPD registered under RNTCP Programme satisfying inclusion and exclusion criteria,
willing to participate in the study will be referred to Ophthalmology OPD and enrolled as cases.
Inclusion criterias:
All patients newly diagnosed with Pulmonary Tuberculosis or Extrapulmonary Tuberculosis.
(1) age greater than 18 years.
(2) patients not yet started on standard treatment for tuberculosis.

10. Exclusion criterias :
Patients with ;
(1) history of optic neuropathy (such as glaucoma, optic neuritis, etc),
(2) history of congenital dyschromatosis (such as colour blindness)
(3) history of retinal diseases;
(4) history of vision abnormalities or visual field defects;
(5) history of drug use inducing ocular toxicity (except ethambutol);
(6) known case of ocular tuberculosis or neurotuberculosis;
(7) known case of MDR or XDR Tuberculosis.

11. Materials
Variables studied
Variables Studied Tools used
Visual Acuity Snellen’s Chart
Relative Afferent Pupilary Defect
(RAPD) - an indicator of optic
nerve damage
Torch Light Examination
Detailed anterior segment
evaluation
Slit Lamp Bio-Microscopy
Examination
Refractive Errors Refraction Testing
Detailed Posterior Segment
Evaluation
Indirect Ophthalmoscopy
Colour Vision Testing Ishihara chart 38 plates edition
RNFL thickness Optical coherence Tomography
(oct) machine – Topcon 3D

12. Topcon 3D OCT Maestro 1

13. • Primary outcome variable
Changes in peripapillary Retinal Nerve Fibre Layer (RNFL) in patients
undergoing ethambutol treatment.
• Secondary outcome variable :
Correlation of degree of retinal nerve fibre layer thinning with vision acuity.

14. 4.5.4 Instruments/questionnaires used for data
collection
• Name -
• Age -
• Sex -
• Address -
• Phone No -
• Occupation -
• Co-morbid Conditions -
• Drug history -
• Duration of Ethambutol Treatment -
• Dose of ethambutol -

15. Detailed research plan
• The study will be carried out in the Department of Ophthalmology in a Tertiary Care Centre
and Institutional Ethical Committee approval will be taken.
• Patients newly diagnosed with Pulmonary/Extrapulmonary Tuberculosis, reporting to Medicine
OPD and Chest and TB OPD registered under RNTCP Programme satisfying inclusion and exclusion
criteria, willing to participate in the study will be referred to Ophthalmology OPD and enrolled as
cases.
• Written Informed Consent will be obtained from all the patients satisfying the inclusion and
exclusion criteria.
• Detailed history covering personal history, occupational history, history of present illness,
history of any co-morbidity and any drug usage will be taken.

16. • Patients will be assessed for below given parameters at Baseline i.e before start of
treatment and after completion of 3 months of ethambutol treatment.
• Results of these parameters at baseline and after completion of 3 months of
ethambutol treatment will be compared for any significant RNFL changes.

17. Parameters Studied Tools used
Visual Acuity Snellen’s Chart
Relative Afferent Pupilary Defect
(RAPD) - an indicator of optic
nerve damage
Torch Light Examination
Detailed anterior segment
evaluation
Slit Lamp Bio-Microscopy
Examination
Refractive Errors Refraction Testing
Detailed Posterior Segment
Evaluation
Indirect Ophthalmoscopy
Colour Vision Testing Ishihara chart 38 plates edition
RNFL thickness Optical coherence Tomography
(oct) machine – Topcon 3D
Following Parameters will be examined:

18. • Data collection procedure: Data will be collected as per the Performa and entered into
excel sheet to be analyzed later.
• Cost involved – As OCT machine is already available for routine workup
• Who is going to bear the cost?
Investigator
• Statistical analysis- Analysis of change in RNFL thickness will be done by paired T test.

19. References
• Global tuberculosis report 2019. License: CC BY-NC-SA 3.0 IGO. Geneva: World Health
Organization, 2019.
• Chaudhuri AD. Recent changes in technical and operational guidelines for tuberculosis control
programme in India-2016: a paradigm shift in tuberculosis control. J Assoc Chest Physicians
2017 Jan 1; 5: 1.
• Ezer N, Benedetti A, Darvish-Zargar M, Menzies D. Incidence of ethambutol-related visual
impairment during treatment of active tuberculosis. Int J Tubercu Lung Dis. 2013 Feb; 17(4):
447–455
• Leibold JE. The ocular toxicity of ethambutol and its relation to dose. Ann N Y Acad Sci
1966;135:904–9.
• Kahana LM. Toxic ocular effects of ethambutol. CMAJ 1987;137:213–6.
• Grzybowski A, Zülsdorff M, Wilhelm H, et al. Toxic optic neuropathies: an updated review. Acta
Ophthalmol 2015;93:402–10.

20. References
• Chamberlain PD, Sadaka A, Berry S, et al. Ethambutol optic neuropathy. Curr Opin
Ophthalmol. 2017;28(6):545 –51.
• Fraunfelder FW, Sadun AA, Wood T. Update on ethambutol optic neuropathy. Expert Opin
Drug Saf 2006;5:615–8.
• Woung LC, Jou JR, Liaw SL. Visual function in recovered ethambutol optic neuropathy. J Ocul
Pharmacol Ther 1995;11:411–9.
• Kumar A, Sandramouli S, Verma L, et al. Ocular ethambutol toxicity: is it reversible? J Clin
Neuroophthalmol 1993;13:15–17.
• Stefan W. Hell, Robert N. Weinreb, Josef F. Bille, High Resolution Imaging in Microscopy and
Ophthalmology, Optical Coherence Tomography (OCT): Principle and Technical Realization,
Cham, Switzerland, y Springer Nature Switzerland AG.
• Mandal S, Saxena R, Dhiman R, et al. Br J Ophthalmol 26 Juluy 2020 . doi:10.1136/
bjophthalmol-2020- 316897
• Menon V, Jain D, Saxena R, et al. Br j Ophthalmol 15 Nov 2014.doi:10.1136/bjo.2008.148502

21. PARTICIPANT INFORMATION SHEET (PIS)
GUIDELINES FOR DESIGNING PARTICIPANT INFORMATION SHEET
1. Study Title - Evaluation of Retinal Nerve Fibre layer (RNFL) thickness using Optical Coherence
Tomography (OCT) in patients undergoing ethambutol treatment.
2. Aim and methods of the research study - There is thinning of retinal nerve fibre layer with an increase in
duration or dose of treatment with ethambutol . If the RNFL thinning is detected at an early stage, irreversible
visual loss can be prevented. We recommend careful interpretation of RNFL data on individuals undergoing
ethambutol treatment when applying the current available OCT nomograms.
3. Expected duration of participation - 2 visits to Ophthalmology OPD.
4. The benefits to be expected from the research to the participant or to others - To detect ocular toxicity
at an early stage due to ethambutol treatment using OCT and prevent irreversible visual loss.

22. 5. Description of Diagnostic Test/ Procedure that the participant will be subjected to in layman’s language –
I) Vision Testing
II) Torch light examination- Pupillary changes evaluation
III) Slit lamp bio-microscopy examination – Detailed Eye Evaluation
IV) Test to decide spectacle prescription
V) Test to evaluate Retina using Indirect Ophthalmoscopy to rule out ocular Tuberculosis or any other pathology.
VI) Colour Vision testing using Ishihara 38 plates edition.
VII) Optical Coherence tomography (OCT)- Detailed evaluation of Retina
The above given examinations will be done before start of treatment and at the end of 3 months of ethambutol
treatment.
6. Any risk or discomfort to the participant associated with the study - None
7. Your records will be strictly confidential
8. Provision of free treatment for research related injury - Not applicable

23. 9. Compensation of subjects for disability or death resulting from such injury - Not applicable
10. Amount of blood sample (quantity in tea spoon full) to be taken - Not applicable.
11. Costs and source of investigations, disposables, implants and drugs/ contrast media – 1650 Rs /-
12. In case of a drug trial: a. The chemical name of the drug, date of its manufacturing and batch
number must be mentioned - Not applicable
13. You are free to withdraw from research at any time without penalty or loss of benefits to which you
would be entitled otherwise
Telephone number/ contact number of Principal investigator and Co-Investigator – Principal Investigator
- 9665343366
Contact number of the head of the institute (in case of complaints)

24. Consent form
I, Mr./ Mrs. ___________________________________, age ______ years residing at
_________________________________________________________________
hereby give my
informed consent to participate in the project.
1. There is no compulsion on me to participate in this project and I am giving my
free
consent for it.
2.I am ready and willing to undergo all tests and treatments in the present project.
3.I have read and I have been explained the general information and purpose of
the present project.
4.I have been informed / I have read the probable complications while participating
in the present project.
5.I know that I can withdraw from the present project at any time.
6.Any data or analysis of this project will be purely used for scientific purpose and
my name will be kept confidential except when requireranylegalpurpose.
7. I can read English / I can understand data read out to me in English.
2/2020
ane/MIMER
24

25. 25
INFORMED CONSENT FORM
(Marathi)
सूचित सहमचत प्रपत्र
1. मी, श्री./श्रीमती ____________________________________, वय ______ वर्षे
_________________________________________________________________ येथे
राहतो
व त्याद्वारे ________________________________________________________या
प्रकल्पात भागघेण्यासाठी तयारआहे.
2. या प्रकल्पात भागघेण्यासाठी माझ्यावर कोणतीही सक्ती नाहीआणण मी माझे त्यासाठी संमती.
देतआहे
3. प्रकल्पातील सववचाचण्या आणण उपचारांचा सामना करण्यास तयारआहे.
4. मी वाचले आहे आणण मला प्रकल्पाची सववसाधारण माणहती आणण उद्देश समजावून सांणगतले
आहे.
5.मला माणहतआहे कीमी प्रकल्पातून कधीही माघार घेऊशकतो.
6. या प्रकल्पाचा कोणताही डेटा णक
ं वा णवश्लेर्षण पूणवपणे वैज्ञाणनक हेतू साठी वापरले जाईल आणण
कोणत्याही कायदेशीर हेतू साठीआवश्यक नसल्यास माझे नाव गोपनीय ठे वले जाईल.
तारीख:
सहभागी
साक्षीदारः
1
2
प्रधान अन्वेर्षकांची स्वाक्षरी

26. 2
26
INFORMED CONSENT FORM
(Hindi)
सूचित सहमचत प्रपत्र
संस्थागत नैचतकता सचमचतको अनुसंधानप्रस्ताव प्रस्तुतकरने क
े चिए
1. मैं, श्री / श्रीमती ____________________________________, उम्र ______ वर्षव
________________________________________________________________________
_
पर रहता हं और------------------------------------------------------------- अध्ययनमें भाग लेने क
े
णलए तैयार हं।
2. इस पररयोजना में भाग लेने क
े णलए मुझपर कोई बाध्यता नहीं है और मैं अपना णनःशुल्क दे रहा हं
इसक
े णलए सहमणत।
3. मैं वतवमान पररयोजना में सभी परीक्षणों और उपचारों सेगुजरनेक
े णलए तैयार हं।
4. मैंने पढा हैऔर मुझे वतवमान पररयोजना की सामान्यजानकारी और उद्देश्य समझायागया है।
5. मुझे सूणचत णकयागया है / मैंने वतवमान पररयोजनामें भागलेते समय संभाणवत जणटलतांं को पढा
है।
6. मुझे पता है णकमैं णकसी भी समय वतवमान पररयोजना से हट सकता हं।
7. इस पररयोजनाका कोई डेटा णवश्लेर्षणणवशुद्धरूपसे वैज्ञाणनक उद्देश्यक
े णलए उपयोगणकया
जाएगाऔर णकसी भी कानूनी उद्देश्यक
े णलए आवश्यक होने पर मेरे नामको गोपनीय रखाजाएगा।
णदनांक:
सहभागीका हस्ताक्षर
गवाहों:
1।
2।
प्रधान अन्वेर्षकका हस्ताक्षर

27. THANK YOU